Clinical and Experimental Hepatology最新文献

Aim of the study: To assess the expression of selected miRNAs as predictive factors of hepatological complications in Epstein-Barr virus (EBV)-infected children.

Material and methods: This study included 68 children infected with EBV aged 1 to 18 years hospitalised between 01.12.2018 and 31.12.2020 in the Department of Paediatrics, Infectious Diseases and Hepatology. The expression of 5 miRNAs (miR-122-5p, miR-21-3p, miR-34a-5p, miR-26b-5p, miR-199a-5p) was analysed by real-time PCR using the TaqMan Fast Advanced Master Mix kit.

Results: In the group of EBV-infected children, statistically significantly higher expression for miR-21-3p, miR-122-5p, miR-26b-5p and miR-34a-5p was confirmed. In a group of 54 children diagnosed with hepatitis, along with an increase in alanine aminotransferase (ALT) and g-glutamyl transpeptidase (GGTP) activity, an increase in expression of miR-21-3p, miR-122-5p, miR-26b-5p, miR-34a-5p and miR-199a-5p was observed.

Conclusions: Increased expression of miR-21-3p, miR-122-5p, miR-26b-5p, miR-34a-5p and miR-199a-5p in EBV-infected children appears to be a risk factor for hepatological complications progressing to biliary pole defects.

Aim of the study: Endoscopic ultrasound (EUS)-guided liver biopsy (LB) has become an increasingly popular method of tissue acquisition for evaluating liver diseases. Despite its advantages, EUS-LB has not been widely adopted in clinical practice due to concerns regarding efficacy and safety. Present data on EUS-LB from India are scarce. We aimed to study the diagnostic outcome and safety of EUS-guided liver biopsy.

Material and methods: This is a retrospective analysis of prospectively maintained data from January 2021 to October 2022 of consecutive patients undergoing EUS-LB at four tertiary care centers in India. The primary outcome was sample adequacy, while secondary outcomes were rate of successful pathological diagnoses and incidence of adverse events (AE).

Results: A total of 74 patients (median age: 44.5 years, 50.0% males) were included. The majority of the patients underwent left-lobe biopsy (62/74, 83.7%), and a 19-G Franseen FNB needle was most commonly used (61/74, 82.4%). Wet heparin suction was used in most cases (60/74, 81.1%). There were five mild AEs observed (one case of self-limited bleeding and four cases of post-procedural pain). Adequate and optimal samples were obtained in 71 (95.9%) and 49 (66.2%) cases, with a conclusive diagnosis being made in 97.3% (72/74) of the patients. On multivariate analysis, the presence of ascites was a negative predictor of optimal sample (odds ratio [OR] = 0.128, 95% CI: 0.017-0.96).

Conclusions: EUS-LB is a safe and viable alternative to percutaneous liver biopsy, achieving diagnosis in > 95% of cases. EUS-LB can be performed safely even in patients with mild ascites, although ascites reduces the chances of getting an optimal sample.

Aim of the study: To evaluate the role of hepatic venous pressure gradient (HVPG) measurement in patients with resectable hepatocellular carcinoma (HCC) we describe our experience with the procedure as part of our hospital standard preoperative algorithm. We present our protocol for this situation, the HVPG measurement procedure, and the results of our cohort.

Material and methods: We performed a retrospective statistical analysis of all patients who underwent planned hepatic resection for HCC with HVPG measurement between 1/2016 and 1/2023. The cohort included 35 patients (30 males, mean age 69.5 years) who underwent HVPG measurement before liver resection for HCC.

Results: The success rate of measurement was 91.4%, with serious complications in 2.9% of cases. Due to the clinically significant portal hypertension (CSPH) 31.3% of patients were rejected for resection. Seventeen patients with excluded CSPH underwent resection with one case of a postoperative liver event, liver decompensation, representing 5.9% of them. One patient (5.9%) had a complicated postoperative course with fasciitis. None of the patients who underwent resection (88.2%) was readmitted to the hospital due to surgical complications or a liver event during 90 days of follow-up, and no death was reported. The median overall survival (OS) in the resected subgroup was 70 months (95% CI: 52-86), and in patients rejected for surgery (resection and transplantation) 35 months (95% CI: 13-48).

Conclusions: HVPG measurement is the gold standard for the quantification of portal hypertension. Hepatic vein catheterization is invasive, but a safe procedure, with a clear impact on the management of resectable HCC.

Aim of the study: Currently, there are insufficient scientific data regarding the efficacy and safety of direct oral anticoagulants (DOACs) compared to warfarin in patients with both liver cirrhosis (LC) and atrial fibrillation (AF). The aim of the study was to analyze the frequency and risk factors for the development of thrombotic and hemorrhagic complications in patients with LC and AF after DOAC treatment compared to warfarin.

Material and methods: A randomized clinical trial was conducted including 56 patients with both LC and AF treated with dabigatran (n = 30) and warfarin (n = 26). The frequency and risk factors of hemorrhagic and thrombotic complications were evaluated after 3 months of observation.

Results and discussion: The overall frequency of bleeding was significantly higher after treatment with warfarin (p = 0.038). The frequency of major and minor bleeding events did not differ statistically significantly between the two groups (p > 0.05). Factors which significantly increased the risk of bleeding were: glomerular filtration rate (GFR) < 60 ml/min/1.73 m² (adjusted hazard ratio (AHR) = 0.82, CI: 0.69-0.96, p = 0.02), constant of thrombin activity (CTA) < 25 units of low-frequency piezoelectric thromboelastography (AHR = 0.66, CI: 0.46-0.92, p = 0.017) and prior history of bleeding (AHR = 108, CI: 8.78-134, p < 0.001).

Conclusions: The use of dabigatran in patients with Child-Pugh class A and B of LC and AF has advantages over warfarin, as it is clinically associated with a lower incidence of bleeding. An increased risk of bleeding is observed in patients with LC classes A and B according to the Child-Pugh scale and AF, who have a reduced GFR < 60 ml/min/1.73 m², CTA < 25 units and a prior history of bleeding.

Aim of the study: Liver cancer (hepatocellular carcinoma - HCC) remains a serious health challenge; it is the fourth leading cause of death worldwide. Egypt ranks fifteenth worldwide and the third in Africa in terms of HCC burden. The present study aimed to assess some microRNAs (miRNAs) including miRNA-7, miRNA-10, and miRNA-21, serum markers such as cluster of differentiation-14 (CD-14) and transforming growth factor b1 (TGF-b1), and other biochemical parameters as non-invasive tools for HCC diagnosis.

Material and methods: The study included 100 participants divided into five groups: group I (20 normal subjects as a healthy group), group II (20 participants with chronic HCV infection but non-cirrhotic), group III (20 volunteers with chronic HCV infection and compensated cirrhosis), group IV (20 patients with chronic HCV infection and decompensated cirrhosis), and group V (20 participants with HCC). Levels of miR-7, miR-10, and miR-21 were evaluated using qRT-PCR. Serum ALT, AST, total bilirubin, total protein, albumin, PT, INR, and platelet count were determined. FIB-4 and APRI test levels were also calculated. CD-14 and TGF-β1 serum levels were estimated using enzyme-linked immunosorbent assay (ELISA) kits.

Results: The expression levels of miR-21 followed by miR-10 showed high sensitivity and specificity in predicting HCC. Serum CD-14 and TGF-b1 levels were significantly increased in all patient groups.

Conclusions: From the study, it is concluded that the expression level of miR-21 has the highest sensitivity and specificity, followed by miR-10, which has high sensitivity and low specificity as non-invasive markers for HCC detection, while miR-7 exhibits high sensitivity and reasonable specificity in fibrosis detection.

Aim of the study: Studies comparing atezolizumab plus bevacizumab (ATE/BEV) vs. lenvatinib (LEN) for advanced hepatocellular carcinoma (aHCC) have shown conflicting results. With this background, we aimed to collate the available evidence comparing ATE/BEV and LEN in aHCC.

Material and methods: A comprehensive search of three databases was conducted from inception to November 2022 for studies comparing ATE/BEV with LEN for managing aHCC. Results were presented with their 95% confidence intervals (95% CI) as the hazard ratio (HR) for time-to-event outcomes or odds ratios (OR) for dichotomous outcomes.

Results: A total of 8 studies were included. On analysis of matched cohorts, there was no difference in the objective response rate (ORR) (adjusted odds ratio [aOR] = 1.15, 95% CI: 0.83-1.61) or disease control rate (DCR) (aOR = 0.83, 95% CI: 0.49-1.38) between groups. Three studies reported a significantly longer progression-free survival (PFS) with ATE/LEN, while one reported a longer PFS with LEN. The adjusted hazard ratio (aHR) for PFS available from three studies was comparable (HR = 1.06, 95% CI: 0.75-1.50). Data were insufficient to carry out a formal analysis for overall survival (OS), but none of the studies reported any difference in OS. On comparison of overall adverse events (AE) and ≥ grade 3 AE, there was no difference in the overall analysis, but higher risk of AE with LEN on sensitivity analysis.

Conclusions: Based on the currently available literature, LEN was found to be non-inferior to ATE/BEV in terms of ORR, DCR, and PFS. However, LEN may be associated with a higher incidence of AEs. Further head-to-head trials are required to demonstrate the superiority of ATE/BEV over LEN.

In recent years, the diagnosis and understanding of nonalcoholic fatty liver disease (NAFLD), recently redefined as metabolic dysfunction-associated steatotic liver disease (MASLD), and its relationship with cardiovascular diseases (CVD) are gaining better understanding. As MASLD shares common risk factors with CVD, including obesity, insulin resistance, hypertension, and dyslipidemia, research increasingly identifies it as a potential independent risk factor for CVD. The exact mechanisms linking MASLD to CVD remain complex and multifaceted, involving metabolic, inflammatory, and vascular pathways. Current cardiology guidelines recognize the significant association between MASLD and CVD, advocating its integration into cardiovascular risk assessment and management. Despite the progress, gaps persist in understanding underlying molecular and cellular mechanisms and the representation of diverse populations in epidemiological studies. The review illuminates the clinical implications of the MASLD-CVD link and identifies directions for future research.

Aim of the study: Biliary atresia (BA) is a blockage in the tubes (ducts) that carry bile from the liver to the gallbladder. The aspartate aminotransferase to platelet ratio (APRI), and Fibrosis-4 (FIB-4) scores are commonly used compound surrogates for advanced fibrosis. However, the use of APRI and FIB-4 entails a risk of overestimating the fibrosis stage due to the impact of necroinflammatory activity on transaminases. So, we determined the optimal cutoff values of the APRI and FIB-4 indices in prediction of fibrosis in BA patients. The aim of the study was to evaluate the validity of the APRI and FIB-4 indices in prediction of fibrosis in patients with BA.

Material and methods: A cross sectional hospital-based study was conducted on 121 children complaining of BA attending the National Liver Institute, Menoufia University, Shebin Elkom, Menoufia, Egypt, during the period from January 2022 to February 2023.

Results: The APRI score was significantly higher among neglected BA than BA type II a, BA type III, type II b and type I (p = 0.001). Also FIB-4 was significantly higher among neglected BA than BA type II a, BA type II b, type III and type I (p = 0.001). Receiver operating characteristic (ROC) curve analysis showed that the cutoff point of the APRI score in prediction of fibrosis in patients with BA was 1.29, with sensitivity of 88.6% and specificity of 76.0%, while the cutoff point of FIB-4 in prediction of fibrosis in patients with BA was 9.82 with sensitivity of 89.0% and specificity of 70.0%.

Conclusions: Our study confirms that FIB-4 and APRI scores are both able to predict severe fibrosis. APRI score and FIB-4 are good non-invasive alternatives to liver biopsy in the detection of liver fibrosis and its extent in patients with BA.

Aim of the study: Hepatitis C virus (HCV) is one of the most common causes of liver-related deaths worldwide. Non-hepatic cancers such as lung and pancreatic cancers have been linked to HCV infection. This study aimed to determine whether HCV seropositivity was related to the development of extrahepatic malignancies and whether this had an impact on patients' survival.

Material and methods: This retrospective case control study included 1476 patients with lung, colorectal, pancreatic and breast cancers compared to 1550 age- and sex-matched controls regarding HCV seropositivity. In the cancer group, HCV seropositive and seronegative subjects were compared for TNM staging, histologic grading and survival.

Results: There was no significant difference between cancer patients and controls regarding age and sex. The percentage of HCV seropositivity was significantly higher in the total cancer group compared to that in the control group (11.6% vs. 7.3%) [OR = 1.67, p < 0.001] and in cancer types: lung (20.1%) [OR = 3.20, p < 0.001], colorectal (11.8%) [OR = 1.70, p = 0.025], pancreatic (25.4%) [OR = 4.33, p < 0.001] and breast cancer (8.1%) [OR = 1.47, p = 0.03]. There was a significant decrease in survival among HCV seropositive subjects compared to seronegatives in colorectal [HR = 2.77, p = 0.002] and pancreatic cancer [HR = 2.2, p = 0.004], a non-significant decrease in lung cancer [HR = 1.02, p = 0.93] and a non-significant increase in breast cancer [HR = 0.79, p = 0.51].

Conclusions: HCV seropositivity was associated with increased risk of lung, colorectal, pancreatic and breast cancer development; it was also associated with reduced survival in colorectal and pancreatic but not in lung and breast cancers.

Aim of the study: Despite the excellent effectiveness of direct-acting antivirals (DAA) in the treatment of hepatitis C virus (HCV) infection, still a few percent of patients fail therapy. The study aimed to determine the effectiveness of triple vs double rescue treatment in such a population.

Material and methods: The study included all consecutive DAA-experienced patients retreated with pangenotypic options from the EpiTer-2 database, a retrospective national multicenter real-world project evaluating antiviral treatment in HCV-infected patients in 2015-2023.

Results: The studied population consisted of 269 patients, of whom 208 were treated with the double (P2) and 61 with the triple (P3) pangenotypic option. No statistically significant differences were found between these subpopulations, except a significantly more frequent history of liver transplantation in the P3 group (6.6% vs. 0.5%, p = 0.01). In the P2 group, two-thirds of patients were treated with velpatasvir/sofosbuvir, while in the P3 group the majority of patients received a combination of velpatasvir/sofosbuvir/voxilaprevir. Virological response at the end of therapy was comparable in both analyzed subpopulations, but the sustained virologic response (SVR) rate was significantly higher in triple retherapy, 98.3% vs. 88.7%, p = 0.02, calculated after exclusion of patients lost to follow-up. Lower SVR was achieved in genotype 3-infected men with cirrhosis, 88.9% and 80% in P3 and P2, respectively.

Conclusions: A comparison of double and triple pangenotypic retherapy in patients after failure of DAA therapy showed a higher sustained virological response in the triple option with a comparable response at the end of therapy. The factors reducing the chances of cure were cirrhosis, genotype 3 infection and male gender.